The spectrum of T helper cell (Th) defects observed in the peripheral blood leukocytes (PBL) of asymptomatic HIV-seropositive (HIV+) individuals has now been found to be predictive for time to AIDS diagnosis and time to death. The spectrum of Th defects appears to be attributable to a reversal from a predominance of Th1 over Th2 function to a predominance of Th2 over Th1 function. Thus it maybe that Th1 function is protective whereas Th2 is not. The numbers of individuals and of cohorts of individuals who exhibit potent T activity against HIV antigens but who are seronegative continue to grow and expand. At present, among HIV-exposed but seronegative individuals the percent of HIV-specific Th responsive individuals are: gay men, 63%; intravenous drug users, 45%; accidentally-exposed health care workers, 75%; surviving exposed hemophiliacs, 19%; and newborns of HIV- infected mothers, 35%. The majority of these individuals remains seronegative on follow-up, although a few are PCR+ for HIV DNA. The studies summarized above raised the possibility that cellular immunity, mediated by Th1 cells, is protective, but humoral immunity, mediated by Th2 cells is not. If correct, these findings would indicate that AIDS vaccine development should be directed to augment cellular rather than humoral immunity.